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Long-acting genipin derivative protects retinal ganglion cells from oxidative stress models in vitro and in vivo through the Nrf2/antioxidant response element signaling pathway
- フォーマット:
- 論文
- 責任表示:
- Koriyama, Yoshiki ; Chiba, Kenzo ; Yamazaki, Matsumi ; Suzuki, Hirokazu ; Muramoto, Ken-ichiro ; Kato, Satoru
- 言語:
- 英語
- 出版情報:
- Wiley-Blackwell, 2010-10-01
- 著者名:
Koriyama, Yoshiki Chiba, Kenzo Yamazaki, Matsumi Suzuki, Hirokazu Muramoto, Ken-ichiro Kato, Satoru - 掲載情報:
- Journal of Neurochemistry
- ISSN:
- 0022-3042
- 巻:
- 115
- 通号:
- 1
- 開始ページ:
- 79
- 終了ページ:
- 91
- バージョン:
- author
- 概要:
- 金沢大学医薬保健研究域医学系<br />金沢大学理工研究域電子情報学系<br />Previously, we reported that genipin, a herbal iridoid, had neuritogenic and neuroprotective actions on PC12 cells. Although nitric oxide (NO)-activated signalings were proposed to be neu … ritogenic, the neuroprotective action of genipin remains to be elucidated. From the standpoint of NO activation, we tested a possible protective mechanism through the nitrosative Kelch-like ECH-associated protein (Keap1)/NF-E2-related factor 2 (Nrf2)-antioxidant response element pathway in rat retinal ganglion cells (RGC-5 cells) in culture, and in vivo, against hydrogen peroxide and optic nerve injury (ONI), respectively, using a long-acting (1R)-isoPropyloxygenipin (IPRG001). IPRG001 induced NO generation and the expressions of antioxidative enzymes, such as heme oxygenase-1 (HO-1), in RGC-5 cells. The protective action of IPRG001 depended on HO-1 and NO induction. We found that S-nitrosylation of Keap1 by IPRG001 may contribute to translocation of Nrf2 to the nucleus and triggered transcriptional activation of antioxidative enzymes. Furthermore, apoptotic cells were increased and 4-hydroxy-2-nonenal was accumulated in rat retina following ONI. Pre-treatment with IPRG001 almost completely suppressed apoptosis and accumulation of 4-hydroxy-2-nonenal in RGCs following ONI accompanied by HO-1 induction. These data demonstrate for the first time that IPRG001 exerts neuroprotective action in RGCs in vitro and in vivo, through the Nrf2/antioxidant response element pathway by S-nitrosylation against oxidative stress. © 2010 International Society for Neurochemistry. 続きを見る
- URL:
- http://hdl.handle.net/2297/25490
類似資料:
Wiley blackwell / International Society for Neurochemistry | |
Public Library of Science | |
金沢大学医薬保健研究域医学系 | |
International Society for Neurochemistry / Blackwell Publishing | |